1. Field of the Invention
The present invention is related generally to control of liquid flow from a vessel. More particularly, the invention relates to a bi-directional check valve for use in conjunction with a U-valve for preventing inadvertent self discharge of a liquid from a vessel.
2. Description of the Related Art
One commonly used technique for the control of discharge while reducing the need for complex valve systems is a U-valve arrangement. It is advantageous to provide a U-shaped tube, commonly referred to as a U-valve, at a bottom port of a vessel, in order to prevent the self discharge of liquid from an open bottom port of the vessel. Under ordinary circumstances, the U-shaped tube allows the liquid from the vessel to enter the tube to a level which does not exceed the level of the liquid in the vessel. This arrangement allows the convenient maintenance of equilibrium of liquid level in the vessel, without requiring that a valve at the bottom of the vessel remain closed. It is possible, however, to use such a U-shaped tube to discharge liquid from the vessel by applying a negative pressure to the tube. It is also possible to use the U-shaped tube to purge the vessel by directed gas under positive pressure from the output end of the tube.
A U-valve works reliably with large tubing inner dimensions (IDs), and under room temperature conditions; however, a U-valve based on small ID tubing and operated with sufficiently hot liquids may cause undesired discharge of the contents of a vessel through the U-shaped tubing. This occurs because of increased pressure inside the vessel and the origination of gas bubbles in the fluid under higher temperature conditions. The formation of gas bubbles can cause the level of liquid in the vessel to rise above the level of liquid in the U-shaped tube, resulting in a siphoning effect, which can cause a complete discharge of the liquid from the vessel. Smaller ID tubing may exhibit capillary action, which increases the likelihood of siphoning. Thus, in many cases the U-valve arrangement requires the use of an additional valve or a plurality of additional valves, causing additional expense and increasing the complexity of the system.
The importance of simplicity in chemical systems is readily apparent when considered in the context of parallel chemical reactions. The ability to appropriately manipulate reaction vessels for a plurality of parallel chemical reactions and to provide and evacuate fluids from such vessels is becoming increasingly important. As the number of desired chemical reactions increases, manual or simple mechanical arrangements become impractical. By way of example, combinatorial chemical synthesis permits the production of very large numbers of small molecule chemical compounds which may, for example, be tested for biological activity.
Certain combinatorial synthesis methods employ polymeric resin beads as solid phase substrates upon which the small molecule compounds are formed. In these methods, sometimes referred to as the “mix and split”, and “direct divide” methods, a sample of beads is divided among several reaction vessels and a different reaction is performed in each vessel. The beads from all the vessels are then pooled and/or redivided into a second set of vessels, each of which now contains approximately equal numbers of beads carrying the products of the first set of reactions. When a second reaction is performed, each of the products of the first set of reactions acts as a substrate for a new set of reactions which produce all the possible combinations of reaction products.
The mix and split combinatorial chemical synthesis method is discussed in greater detail in, M. A. Gallop, R. W. Barrett, W. J. Dower, S. P. A. Fodor and E. M. Gordon, Applications of Combinatorial Technologies to Drug Discovery, 1. Background and Peptide Combinatorial Libraries, Journal of Medical Chemistry 1994, Vol. 37, pp. 1233-1251; E. M Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor and M. A. Gallop, Applications of Combinatorial Technologies to Drug Discovery, 2. Combinatorial Organic Synthesis, Library Screening Strategies and Future Directions, Journal of Medical Chemistry 1994, Vol. 37, pp.1385-1401, M. R. Pavia, T. K. Sawyer, W. H. Moos, The Generation of Molecular Diversity, Bioorg. Med. Chem. Lett. 1993, Vol. 3, pp. 387-396 and M. C. Desai, R. N. Zuckerman and W. H. Moos, Recent Advances in the Generation of Chemical Diversity Libraries, Drug Dev. Res. 1994, Vol. 33, pp. 174-188 which are hereby incorporated by reference. See also, U.S. Pat. No. 5,565,324 which is also hereby incorporated by reference. The direct divide method is described in greater detail in U.S. Pat. No. 5,663,046 incorporated by reference herein in its entirety.
By providing an extremely large library of chemical compounds for testing, combinatorial chemical synthesis facilitates the development of compounds which may be used to develop new drugs for treating a wide range of diseases. Rather than painstakingly manually synthesizing chemicals one at a time and individually testing them for biological activity with, for example, an enzyme involved in heart disease, or a cell receptor involved in fighting cancer, many chemicals can be developed and tested in parallel, greatly accelerating the drug development process and, hopefully, leading to major advances in the treatment and prevention of disease.
Unfortunately, the task of simultaneously synthesizing a large number of compounds can involve complex, unwieldy processes and equipment. Generally, reagents and solvents must be added to reaction vessels in precisely timed sequences. Additionally, the temperature of each reaction vessel must often be well-defined and a specific temperature profile may be required for optimal reaction. Typically, the contents of each reaction vessel should be stirred or mixed in order to ensure the proper distribution of reactants.
One conventional approach to delivering fluids to reaction vessels relies upon a labyrinthine plumbing system which routes solvents, reactants and reagents to various reaction vessels through tubes selected by a complex valving system which may be under computer control. A similar system is required to remove the reaction products from vessels. Not only is such a system complex and expensive, it also presents major maintenance, reliability and contamination problems.
For example, all the tube material and the valves which direct flow among the tubes must be maintained on a regular basis. The valve materials may be corroded or otherwise damaged by contact with the reagents, solvents or reaction products and consequently must be vigilantly maintained in order to prevent cross-contamination. Even if the valves and tubes are well-maintained, in light of the diverse range of chemicals that may be involved, there is still a very real threat of corrosion and cross-contamination. Additionally, controlling the timing, mixing, and heating of reactants within such a complex system is a formidable task and, with conventional mixing systems, the beads which provide reaction surfaces often are undesirably ground up to some extent against the bottom of the reaction vessel.
In order to reduce the complex plumbing of valve and tube systems, some systems rely upon robotic arms to deliver reagents into reaction vessels under program control. Although the complexity of the plumbing system is greatly reduced in these systems, the robotic system is highly complex and subject to its own problems. Regular maintenance is required on such systems, spills are an inherent hazard, contamination remains a problem, and it may be difficult to control the temperature of, and to provide proper agitation for, reactants.
Such systems typically include complex valving arrangements for flow control, increasing the cost and complexity of such systems and processes.
There exists, therefore, a need in the art for a simple arrangement to prevent the inadvertent self-discharge of liquid through a U-valve, while allowing gases and liquids to pass through the U-valve when desired, and which can be used in the context of a parallel chemical reaction environment in which many valves may be employed.